Research on bacteria that live within our bodies has progressed in recent years and is gaining respect in the scientific community. Most of these bacteria live in our gut, and scientists think they shape our health in a number of ways – some good and some bad. Dr. Virginia Kraus is currently researching bacteria in her 2-year Arthritis Foundation-funded project, “The Role of Low-Grade Endotoxemia in Osteoarthritis.” Her project looks at one molecule made by harmful bacteria.
Lipopolysaccharide endotoxin (LPS) is a molecule produced by harmful bacteria that most commonly live in the gut and gums. It can make its way from the gut or mouth into the bloodstream where it can cause inflammation in different parts of the body. The inflammation can contribute to diseases such as rheumatoid arthritis, inflammatory bowel disease, type 2 diabetes, and obesity, as well as play a role in the development and progression of osteoarthritis (OA).
Dr. Kraus’ study uses blood from an earlier study that looked at whether an antibiotic, called doxycycline, had an effect on the progression of knee OA in obese women. The women took the antibiotic or placebo for 30 months, giving blood samples every 6 months. The study found that women who took low doses of antibiotic had a lower rate of OA disease progression. The antibiotic slowed the disease progression by blocking an enzyme produced by the body that destroys cartilage. Dr. Kraus wondered whether the antibiotic worked because it changed the population of harmful bacteria living in the gut.
Dr. Kraus and her team took the old blood samples and started measuring the levels of LPS and a biomarker called lipopolysaccharide binding protein (LBP). LBP is a protein made by humans that binds to LPS and causes the body to produce an immune response (like fever and/or inflammation). The team is looking for a relationship between the levels of LPS and LBP and progression of OA by x-ray.
The study is at the halfway point, but so far shows promising results. If the study continues in this direction, it may eventually lead to doctors ordering these tests to see if a patient is at risk for increased disease activity due to harmful bacteria. “If this is the case, the disease activity would be very easy to treat. Antibiotics are not the only way to control bacteria. Patients can clear the bacteria from their systems through exercise, which increases HDL (the “good cholesterol”), combined with eating a high-fiber, low-fat diet,” she said.
Dr. Kraus originally became interested in the role of LPS when she read an academic paper that said you can measure LPS in human blood. Scientists had been using LPS for years as a model for inducing inflammation in laboratory experiments, but didn’t realize it was in people’s blood. The new information led to additional studies. While reading other studies about LPS in humans, she found that high levels of LPS in the blood of people with sepsis (a serious blood infection) were associated with people becoming very sick. Other studies showed that small, but abnormal amounts of LPS did not cause people to feel sick, but could cause them, within as little as 24 hours, to develop diabetes. She realized that LPS was playing an important role in disease. “The good thing is,” she said, “that it can be measured and treated.”
Dr. Kraus is a rheumatologist and professor of medicine, pathology, and orthopedic surgery at Duke University School of Medicine in North Carolina. She is also a member of the Duke Molecular Physiology Institute. She has 20 years of experience in OA research.